GASTROINTESTINAL DRUGS Introduction Gastrointestinal Drug Groups Management of Gastrointestinal Disorders Introduction This chapter describes the principal drugs used in the treatment of gastrointestinal disorders, and the choice of treatment for some of the main disorders. Gastrointestinal Drug Groups Antacids Antacids are basic compounds which neutralise hydrochloric acid in the gastric secretions. They are used in the symptomatic management of gastrointestinal disorders associated with gastric hyperacidity such as dyspepsia , gastro-oesophageal reflux disease , and peptic ulcer disease . Antacids do not reduce the volume of hydrochloric acid secreted and elevation of the gastric pH may actually promote an increase in acid and pepsin secretion. However, this is usually minor and short-lived except after large doses of calcium carbonate. Antacids are normally given between meals and at bedtime when symptoms of gastric hyperacidity usually occur; the presence of food in the stomach can prolong the neutralising activity. Some calculate doses as mEq or mmol of acid-neutralising capacity, but the relationship between neutralising capacity and beneficial effect is not straightforward. Other factors, including formulation (liquid preparations are more effective than solids) and duration of action (relatively insoluble antacids are longer acting) are also important. Aluminium salts tend to produce constipation and to delay gastric emptying, while magnesium salts have the reverse effect; a combination of the two may reduce adverse gastrointestinal effects. Another advantage of combined antacid formulations is that a slow-acting antacid such as aluminium hydroxide may be combined with a more rapidly acting drug such as magnesium hydroxide to improve the onset and duration of effect. Alternatively, complexes containing both aluminium and magnesium may be used, such as almasilate, hydrotalcite, and magaldrate. Other drugs that may be combined with antacid formulations include simeticone, which acts as a defoaming agent to reduce excess gas in the stomach, and alginates, which form a gel or foam on the surface of the stomach contents thereby impeding reflux and protecting the oesophageal mucosa from acid attack. Calcium carbonate and sodium bicarbonate are both rapidly acting but have disadvantages: calcium carbonate is usually reserved for short-term treatment because of the risks of rebound acid secretion and metabolic alkalosis, while sodium bicarbonate is absorbed and is contra-indicated in patients who must control sodium intake (e.g. in heart failure, hypertension, renal failure, cirrhosis, or pregnancy). Antacids may interact with numerous other drugs, affecting the rate and extent of their absorption, and in some cases their renal elimination. Changes in gastric pH affect the dissolution of other drugs, and together with altered gastric emptying can markedly influence absorption. Aluminium compounds in particular are noted for their propensity to adsorb other drugs and to form insoluble complexes that are not absorbed. Antacids that alter urinary pH will affect renal clearance of drugs that are weak acids or bases. Several mechanisms may play a part in any particular interaction. Interactions can be minimised by giving antacids and other medication 2 to 3 hours apart. Antacids in this chapter include aluminium salts, magnesium salts, and calcium carbonate. For sodium bicarbonate, see . Drugs in this group include Aceglutamide Aluminium, Alexitol Sodium, Almagate, Almasilate, Aloglutamol, Aluminium Glycinate, Aluminium Hydroxide, Aluminium Hydroxide-Magnesium Carbonate Co-dried Gel, Aluminium Phosphate, Aluminium Sodium Silicate, Basic Aluminium Carbonate, Bismuth Compounds, Calcium Carbonate, Dihydroxyaluminum Sodium Carbonate, Hydrotalcite, Magaldrate, Magnesium Carbonate, Magnesium Hydroxide, Magnesium Oxide, Magnesium Trisilicate, Antidiarrhoeals Antidiarrhoeals are used as adjuncts in the symptomatic treatment of diarrhoea , although the main aim in the management of acute diarrhoea is the correction of fluid and electrolyte depletion with rehydration therapy; this is especially important in infants and young children and antidiarrhoeals are not generally recommended for this age group. Their use is also limited in chronic diarrhoea since treatment aimed at the underlying disorder will often alleviate the diarrhoea. Described in this chapter are drugs which reduce intestinal motility such as the opioid analogues diphenoxylate and loperamide, and adsorbents such as attapulgite and kaolin. Bulking agents (which include bran and ispaghula) have also been used for diarrhoea and for adjusting faecal consistency in patients with colostomies. Drugs in this group include Albumin Tannate, Attapulgite, Bismuth Compounds, Bran, Chalk, Difenoxin, Diphenoxylate, Ispaghula, Kaolin, Lidamidine, Loperamide, Racecadotril, Zaldaride, Antiemetics Antiemetics are a diverse group of drugs used to treat or prevent nausea and vomiting, including that associated with cancer therapy, anaesthesia, and motion sickness . The choice of drug depends partly on the cause of nausea and vomiting. For example, hyoscine or an antihistamine are used in motion sickness whereas dopamine antagonists (such as metoclopramide and domperidone) and 5-HT(3) antagonists (such as ondansetron) are ineffective. Conversely, nausea and vomiting associated with cancer chemotherapy is often hard to control and special regimens have been devised including the use of metoclopramide in high doses, dexamethasone, and, more recently, the 5-HT(3) antagonists. Drugs in this group include Alizapride, Azasetron, Bromopride, Cerium Oxalate, Clebopride Malate, Difenidol, Dolasetron, Domperidone, Dronabinol, Ginger, Granisetron, Itopride, Metoclopramide, Metopimazine, Nabilone, Ondansetron, Ramosetron, Tropisetron, Antisecretory drugs Antisecretory drugs are used in the treatment and prophylaxis of peptic ulcer disease ; some are also employed in other disorders associated with gastric hyperacidity such as gastro-oesophageal reflux disease and dyspepsia and ). They may be divided into: Histamine H(2)-receptor antagonists (H(2)-antagonists), which act by blocking histamine H(2)-receptors on gastric parietal cells, thereby antagonising the normal stimulatory effect of endogenous histamine on gastric acid production. Those described in this chapter include cimetidine, famotidine, nizatidine, and ranitidine. Proton pump inhibitors, which act by blocking the enzyme system responsible for active transport of protons into the gastrointestinal lumen, namely the hydrogen/potassium adenosine triphosphatase (H(+)/K(+) ATPase) of the gastric parietal cell, also known as the `proton pump'. Those described in this chapter include lansoprazole, omeprazole, pantoprazole, and rabeprazole. Selective antimuscarinics, which block cholinergic stimulation of gastric acid production with fewer adverse effects than standard antimuscarinics , but have already largely been superseded. Pirenzepine is an example. Prostaglandin analogues, which inhibit gastric acid secretion by a direct action on the parietal cell and may also inhibit gastrin release and possess cytoprotective properties. Misoprostol is an example. Drugs in this group include Cimetidine, Ebrotidine, Esomeprazole, Famotidine, Lansoprazole, Niperotidine, Nizatidine, Omeprazole, Pantoprazole, Rabeprazole, Ranitidine, Roxatidine, Urogastrone, Laxatives Laxatives (purgatives or cathartics) promote defaecation and are used in the treatment of constipation and for bowel evacuation before investigational procedures, such as endoscopy or radiological examination, or before surgery. Laxatives are frequently employed for self-medication and may sometimes be abused. Abuse of laxatives is a well-known phenomenon that may occasionally lead to toxicity. Laxatives may be classified according to their mode of action. There is, however, a degree of overlap between the various groups and in some cases the precise mechanisms of action are not fully understood. Many traditionally used laxatives have fallen from use owing to the violence of their action or their adverse effect profile. Bulk laxatives (bulk-forming laxatives or bulking agents) cause retention of fluid and an increase in faecal mass resulting in stimulation of peristalsis. Owing to their hydrophilic nature, bulk laxatives may also be used to control diarrhoea and to regulate the consistency of effluent in colostomy patients. Those described in this chapter include bran, ispaghula, and sterculia. Stimulant laxatives (contact laxatives) act by directly stimulating nerve endings in the colonic mucosa, thereby increasing intestinal motility. It is this group of laxatives which is most commonly associated with abuse. Those described in this chapter include bisacodyl, cascara, phenolphthalein, senna, and sodium picosulfate. Osmotic laxatives act by increasing intestinal osmotic pressure thereby promoting retention of fluid within the bowel. Those described in this chapter include saline laxatives such as magnesium citrate, magnesium hydroxide, and sodium sulfate (for magnesium sulfate and sodium phosphate see and respectively). Lactulose may also be classified as an osmotic laxative because its breakdown products exert a similar effect. Also included in this group are the hyperosmotic laxatives such as glycerol and sorbitol , and the macrogols . Faecal softeners (emollient laxatives) are claimed to act by decreasing surface tension and increasing penetration of intestinal fluid into the faecal mass. Those described in this chapter include docusate (which is also believed to have a stimulant action). For the lubricant laxative liquid paraffin see . Drugs in this group include Aloes, Aloin, Bisacodyl, Bisoxatin, Bran, Buckthorn, Casanthranol, Cascara, Cassia Pulp, Colocynth, Croton Oil, Dantron, Docusates, Euonymus, Fig, Frangula, Ipomoea, Ispaghula, Jalap, Lactitol, Lactulose, Liquorice, Magnesium Citrate, Magnesium Hydroxide, Magnesium Oxide, Manna, Oxyphenisatine, Pentaerythritol, Phenolphthalein, Polycarbophil Calcium, Potassium Acid Tartrate, Prune, Psyllium Seed, Rhubarb, Senna, Sodium Picosulfate, Sodium Potassium Tartrate, Sodium Sulfate, Sodium Tartrate, Sterculia, Tamarind, Mucosal protectants Cytoprotective drugs (mucosal protectants) play a role in the management of peptic ulcer disease . They may be divided into: Chelates or complexes, which coat the gastric mucosa preferentially at sites of ulceration by forming an adherent complex with proteins. Those described in this chapter include sucralfate and tripotassium dicitratobismuthate (which also has an antibacterial role in regimens aimed at eradicating Helicobacter pylori). Miscellaneous drugs include liquorice and its derivatives, such as carbenoxolone, which may act by stimulating the synthesis of protective mucus. Drugs in this group include Benexate, Carbenoxolone, Cetraxate, Ebrotidine, Ecabet, Enoxolone Aluminium, Gefarnate, Irsogladine, Liquorice, Plaunotol, Polaprezinc, Rebamipide, Sucralfate, Sulglicotide, Teprenone, Tripotassium Dicitratobismuthate, Troxipide, Prokinetic drugs Prokinetic drugs stimulate the motility of the gastrointestinal tract. Gastrointestinal smooth muscle exhibits intrinsic motor activity which is modified by autonomic innervation, local reflexes, and gastrointestinal hormones. This activity produces peristaltic waves, which move the gut contents from stomach to anus, and segmentations, which encourage digestion. Prokinetic drugs may act at various points within this complex system to enhance gastrointestinal movement. Those described in this chapter include metoclopramide, cisapride, and domperidone. Other drugs with prokinetic properties include parasympathomimetics such as bethanechol or neostigmine , and the macrolide antibiotic erythromycin . Drugs in this group include Bromopride, Cinitapride, Cisapride, Clebopride, Domperidone, Itopride, Metoclopramide, Mosapride, Renzapride, Tegaserod, Management of Gastrointestinal Disorders The management of some gastrointestinal disorders is discussed below. Aspiration syndromes Regurgitation and aspiration of gastric contents (Mendelson's syndrome) is an important cause of morbidity and mortality associated with anaesthesia, especially in obstetrics and in emergency surgery. Chemical pneumonitis and respiratory distress result from the acid aspiration, the risk of which is increased by the drugs given as adjuncts to anaesthesia such as opioid analgesics and atropine.

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